Trends in vehicle control show an increasing reliance on data aggregation and model-based predictive control to improve vehicle performance. The data and models that underly this trend, when analyzed experimentally on-the-road, allow discovery of route and location-specific effects that are not typically captured with generic vehicle or road representations. The influence of these effects on the performance, fuel economy, and stability of vehicle systems - particularly heavy vehicles used individually or in platoons - is poorly understood. This thesis examines the location-specific variations and influences that affect the performance in terms of fuel economy of heavy-duty trucks in urban and highway routes. The methods are motivated by experimental data collection from large numbers of repeated route traversals, with data including vehicle position, speed, acceleration, fuel use as well as drag reduction for following trucks in the case of platooning. These measurements allow the dynamic fuel consumption to be matched as a function of distance along the route as measured in a spatial s-coordinate. Testing situations include conventional single-vehicle operation across a wide range of urban, arterial, and highway situations, as well as the platooning of two trucks on an interstate highway. The results demonstrate that terrain and position information within a route offer significant predictions in terms of fuel economy in a vehicle. Additionally, infrastructure elements, specifically vehicle-to-infrastructure (V2I) communication can be used not only to monitor route information, but also used by the infrastructure to constrain or define behaviors of the vehicle. Moreover, the geometric definition of a road was seen to change the behavior of the stability of a truck platoon. Also, the drag reduction experienced by truck platoon is quantified using wind-tunnel experiments. Afterwards, a framework is proposed where the number of route traversals needed to define a route in terms of fuel use and vehicle speed is obtained based on statistical confidence. Finally, two commercial Volvo trucks are used to obtain location-specific fuel consumption and drag estimates when undergoing a fixed gap-distance in a truck platoon on Interstate-99. When the inter-vehicle platoon spacing was fixed to a one vehicle length, the fuel consumption reduction had a per-route average improvement of 13.6% on one route, and 9.1% on another route. Advisors/Committee Members: Sean Brennan, Dissertation Advisor/Co-Advisor, Sean N Brennan, Committee Chair/Co-Chair, Hosam Kadry Fathy, Committee Member, Stephanie Stockar, Committee Member, Eric Norman Johnson, Outside Member, Karen Ann Thole, Program Head/Chair.